In continuing studies of the role of neuropeptides in the pathophysiology of obsessive-compulsive disorder (OCD) and anxiety, we have demonstrated reduced hormonal and metabolic responsivity to exercise stress during lactation, a period associated with increased central secretion of oxytocin. This suggests that oxytocin may restrain stress and anxiety systems and extends our previous findings of increases in CSF oxytocin in OCD patients after clomipramine treatment. In another clinical study, OCD patients did not have impairment of frontal cortex mediated working memory span or recognition memory, despite multiple imaging studies reporting altered frontal cortex activity in OCD patients. In preclinical animal model studies, we found that Fawn-Hooded rats, a strain with impaired capacity for neuronal serotonin storage, had increased expression of corticotropin-releasing hormone mRNA in the amygdala, where this peptide is known to potentiate fear behavior.